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Conference Report on Contractures in Musculoskeletal and Neurological Conditions

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Conference Report on Contractures in Musculoskeletal and Neurological Conditions Received: 31 July 2019 Revised: 3 January 2020 Accepted: 23 February 2020 DOI: 10.1002/mus.26845 ISSUES & OPINIONS Conference report on contractures in musculoskeletal and neurological conditions Glen H. Nuckolls PhD1 | Kathi Kinnett MSN, APRN2 | Sudarshan Dayanidhi PT, PhD3 | Andrea A. Domenighetti PhD3 | Tina Duong MPT4 | Yetrib Hathout PhD5 | Michael W. Lawlor MD, PhD6,7 | Sabrina S. M. Lee PhD8 | S. Peter Magnusson PT, DMSc9,10,11 | Craig M. McDonald MD12,13 | Elizabeth M. McNally MD, PhD14 | Natalie F. Miller DPT15 | Bradley B. Olwin PhD16 | Preeti Raghavan MD17 | Thomas J. Roberts PhD18 | Seward B. Rutkove MD19 | John F. Sarwark MD20 | Claudia R. Senesac PT, PhD21 | Leslie F. Vogel MS PT22 | Glenn A. Walter PhD23 | Rebecca J. Willcocks PhD21 | William Z. Rymer MD, PhD3 | Richard L. Lieber PhD3 1Division of Neuroscience, National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 2Parent Project Muscular Dystrophy, Hackensack, New Jersey 3The Shirley Ryan AbilityLab, Chicago, Illinois 4Department of Neurology, Stanford University, Palo Alto, California 5School of Pharmacy and Pharmaceutical Sciences, Binghamton University, Johnson City, New York 6Department of Pathology and Laboratory Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin 7Neuroscience Research Center, Medical College of Wisconsin, Milwaukee, Wisconsin 8Physical Therapy and Human Movement Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois 9Department of Physical and Occupational Therapy, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark 10Institute of Sports Medicine Copenhagen, Bispebjerg Hospital, Copenhagen, Denmark 11Department of Orthopedic Surgery, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark 12Department of Physical Medicine & Rehabilitation, University of California Davis School of Medicine, Sacramento, California 13Department of Pediatrics, University of California Davis School of Medicine, Sacramento, California 14Center for Genetic Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois 15Center for Gene Therapy, Nationwide Children's Hospital, Columbus, Ohio 16Department of Molecular, Cellular, and Developmental Biology, University of Colorado at Boulder, Colorado 17Rusk Rehabilitation, New York University School of Medicine, New York, New York 18Ecology and Evolutionary Biology, Brown University, Providence, Rhode Island 19Department of Neurology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 20Department of Orthopaedic Surgery, Northwestern University Feinberg School of Medicine, Chicago, Illinois 21Physical Therapy Department, College of Public Health and Health Professions, University of Florida, Gainesville, Florida 22Department of Rehabilitation, Seattle Children's Hospital, Seattle, Washington 23Department of Physiology and Functional Genomics, University of Florida, Gainesville, Florida Abbreviations: CP, cerebral palsy; DMD, Duchenne muscular dystrophy; ECM, extracellular matrix; EIM, electrical impedance myography; LMN, lower motor neuron; ROM, range of motion; UMN, upper motor neuron. Muscle Nerve. 2020;1–5. wileyonlinelibrary.com/journal/mus © 2020 Wiley Periodicals, Inc. 1 2 NUCKOLLS ET AL. Correspondence Glen H. Nuckolls, PhD, National Institute of Abstract Neurological Disorders and Stroke, 6001 Limb contractures are debilitating complications associated with various muscle and Executive Blvd, Bethesda, MD 20892. Email: [email protected] nervous system disorders. This report summarizes presentations at a conference at the Shirley Ryan AbilityLab in Chicago, Illinois, on April 19–20, 2018, involving researchers Funding information This workshop was supported by National and physicians from diverse disciplines who convened to discuss current clinical and Institute of Child Health and Human preclinical understanding of contractures in Duchenne muscular dystrophy, stroke, Development, National Institute of Neurological Disorders and Stroke, Parent cerebral palsy, and other conditions. Presenters described changes in muscle architec- Project Muscular Dystrophy, and Shirley Ryan ture, activation, extracellular matrix, satellite cells, and muscle fiber sarcomeric structure AbilityLab that accompany or predispose muscles to contracture. Participants identified ongoing and future research directions that may lead to understanding of the intersecting fac- tors that trigger contractures. These include additional studies of changes in muscle, tendon, joint, and neuronal tissues during contracture development with imaging, molecular, and physiologic approaches. Participants identified the requirement for improved biomarkers and outcome measures to identify patients likely to develop con- tractures and to accurately measure efficacy of treatments currently available and under development. KEYWORDS cerebral palsy, contracture, Duchenne muscular dystrophy, muscle, stroke 1 | PURPOSE OF THE WORKSHOP factors are present. Joint pain can be a predictor and/or consequence of contractures in some patients.4,5 Contractures cause significant burden on A research conference was held at the Shirley Ryan AbilityLab in patients due to altered body positioning, decreased independence in per- Chicago, Illinois on April 19–20, 2018, to discuss the causes and treat- forming activities of daily living, and reduced community participation con- ments of contractures, debilitating consequences of a wide range of tributing to social isolation and decreased quality of life. conditions including primary myopathies such as Duchenne muscular dystrophy (DMD), and neurological conditions that affect muscle such as stroke and cerebral palsy (CP). Presenters from the meeting are 3 | CONTRACTURES IN DMD authors of this article. The goals of the meeting were to promote dis- cussion and collaboration among researchers with diverse expertise, Muscular dystrophies are associated with muscle weakness and the gain insights into the causes of contractures, assess biomarkers and replacement of muscle by fat and fibrotic tissue, which contributes to current treatments, and identify gaps in understanding that, if contractures in some patients.2 Researchers studying the natural history addressed, could lead to more effective evidence-based treatments. of DMD discussed data on the patterns of contracture involvement and progression. Altered gait biomechanics resulting from weakness in knee and hip extensors increases the risk that individuals will develop ankle 2 | CONTRACTURES AND PATIENT equinus contracture prior to loss of ambulation, but wheelchair reliance IMPACT is most frequently the result of muscle weakness rather than contrac- tures.6 Contractures develop in the hips and knees in individuals who are There is no universally accepted definition of limb contracture, but reduced nonambulatory when static positioning is more prevalent and weakness range of motion (ROM) accompanied by increased mechanical resistance does not allow full movement against gravity.6-8 Subsequent upper at the ends of the available range are accepted clinical signs. Contractures extremity weakness leads to static positioning and contractures in the in neuromuscular conditions are associated with reduced muscle belly elbows and wrists. The inability of muscles to move a joint through the length, while tendon length is less affected.1-3 Among the neurological and full ROM predisposes the joint to contracture.2 Imbalance in the strength musculoskeletal conditions associated with contracture, the effects on of opposing agonist and antagonist muscles may contribute to this inabil- muscle vary. Some conditions cause muscle hyperactivity, while others ity in some conditions, although in DMD there is no association between cause paralysis or degeneration of muscle fibers and replacement by muscle strength imbalance around a joint and contracture frequency or noncontractile tissue. Muscle weakness or hyperactivity can increase joint severity.6 Contracture progression in DMD is further complicated by static positioning, which may trigger contractures if other predisposing muscle fiber degeneration and tissue fibrosis.2 Mouse models of NUCKOLLS ET AL. 3 muscular dystrophies exhibit progressive muscle weakness and some angles that determine ROM and contracture severity. Video-based exhibit muscle fibrosis, but dystrophic mice do not develop obvious con- motion analysis is also used to measure ROM. Other clinical devices tractures. Presenters described considerable variability in contracture for- used to measure muscle biomechanical properties were discussed, mation in people living with DMD. For example, 50% of participants in including the myotonometer to measure muscle tone for individuals an ongoing study of MRI biomarkers developed knee contractures >20 with UMN signs.14 Ultrasound can measure tendon and muscle kine- soon after loss of ambulation; however, 20% of participants maintained matics, in particular fascicle length and pennation angle in real time full ROM. (R. Willcocks, unpublished data, collected 2010-2018, commu- during static and dynamic tasks. Ultrasound shear wave elastography nicated June 2019). Additional studies are required to identify genetic provides an indirect estimate of tissue stiffness in localized muscle and/or environmental factors that allow some patients to avoid regions.15 Electrical impedance myography (EIM), which assesses the contractures. muscle-induced alteration in a surface-applied current, is sensitive to myofiber cross-sectional area16 and thus has
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